The Neuropathology and Genetics (NPG) Core will perform laboratory analyses on biological fluids collected from living subjects and brain tissue collected at autopsy of participants in the Mayo Alzheimer Disease Research Center (ADRC). The data will be communicated to the Clinical Core using standardized protocols and procedures. The NPG Core will also provide neuropathologic diagnoses and support to research projects related to Alzheimer's disease at the Mayo Clinic. The specific aims are: 1.) Perform brain autopsies on participants of the ADRC. 2.) Provide neuropathologic evaluations and collect neuropathologic data using standardized neuropathologic methods for gross dissections and neurohistology. 3.) Photograph, map and measure vascular lesions and reach consensus about the clinical significance of vascular lesion to cognitive impairment with regular videoconferences and quarterly clinicopathological conferences in Rochester. 4.) Perform immunostaining with antibodies to alpha-synuclein on all cases with either neuronal loss in the substantia nigra or Lewy bodies. 5.) Characterize non- Alzheimer dementia cases with immunocytochemistry and electron microscopy and provide DNA and tissue samples on these cases to Dr. Mike Hutton who is studying biochemistry and genetics of non-Alzheimer dementias. 6.) Provide fixed and frozen brain samples to Project 1 (PI: Dr. S.-H. Yen). 7.) Quantify postmortem white matter pathology with image analysis for correlative studies in Project 3 (PI: Dr. C.R. Jack). 8.) Perform ELISA assays for A-beta of postmortem brain tissue to estimate amyloid burden for correlative studies. 9.) Provide clinically and pathologically well-characterized tissue samples for research on other projects of Mayo investigators. 10.) Bank blood and CSF and perform apolipoprotein-E genotyping on all subjects in the ADRC. Provide plasma samples to Dr. S.G.Younkin for A-beta assays that are integral to his other research projects.